Biochem 501 Lecture 23: Gluconeogenisis

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  1. Lowest possible blood glucose level
    • 1.5 mM, any lower causes coma
    • Too high also = coma
  2. Gluconeogenisis
    • Formation of glucose from non-hexose precursors
    • Found in all organisms
  3. Gluconeogenisis Components for Animals
    • Lactate, Pyruvate, Glycerol, most Amino Acids
    • Takes place in liver/kidney (lesser)
  4. Gluconeogensis components for Plants
    Fats and Proteins (acetyl-CoA from beta oxidation)
  5. Can fatty acids be a substrate for net glucose production?
    • No, going through Kreb's cycle has no net carbon flux
    • The process of beta-oxidation and TCA cycle DOES make energy for gluconeogensis though
  6. Where do carbons in Gluconeogenisis come from?
    Amino Acids
  7. Proteins must be turned to what to be used for Gluconeogenisis
    Amino acids, then Pyruvate
  8. Best way to turn Amino Acids into useful things?
    • Transaminiation
    • Alanine can become Pyruvate
  9. Sources of Glycerol for Gluconeogenisis
    Adipose cells contain triacylglycerol, lipase cuts off Glycerol tip, liver turns Glycerol into dihydroxyacetone phosphate by phosphorylating and then oxidating
  10. Gluconeogenisis is similar to what other process
    Glycolysis, almost exactly same but backwards and uses other enzymes at "irreversible" steps
  11. Gluconeogenisis Bypass 1
    Image Upload 1

    • Enzyme One: Pyruvate Carboxylase
    • Enzyme Two: PEP Carboxykinase
    • Occurs in Mitochondria
  12. Alternate path to PEP
    • Pyruvate ->Oxaloacetate -> Malate -> Oxaloacetate -> PEP
    • PEP formed outside Mitochondria
  13. Sources of Lactate
    • Pyruvate is turned into lactate via fermentation
    • This is called Cori cycle (Glucose to Pyruvate to Lactate to Glucose)
  14. Liver turns Lactate into
  15. Bypasses 2 and 3
    Image Upload 2
  16. Regulation of Gluconeogenesis/Glycolysis
    • Reciprocal Regulation:
    • -High Energy: Stimulates gluconeogenesis
    • -Low Energy: Stimulates glycolysis

    • Major Control Points:
    • F-6-P <--> F-1,6,bis-P
    • -AMP/ATP ration should push either way
    • -Not enough by self
  17. Phosphofructokinase (PFK-1) (nature and inhibitor)
    • Allosteric protein
    • Turns Fruc-6-P and ATP into Fruc-1,6-bisP and ADP
    • Rate-limiting step in glycolysis
    • Inhibited by high levels of ATP (binds active and allosteric site)
  18. Most Important Regulator of Gluconeogensis/Glycolysis
    • Fruc-2,6,-bisP
    • -Activates PFK1 (-> Glycolysis)
    • -Inhibits FBPase1 (x Gluconeogenisis)
    • Tandem Enzymes (PFK2/FBPase2) create and destroy F-2,6-BP respectively
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Biochem 501 Lecture 23: Gluconeogenisis
Biochem 501
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